Maprotiline, sold under the brand name Ludiomil among others, is a tetracyclic antidepressant (TeCA) that is used in the treatment of depression. It may alternatively be classified as a tricyclic antidepressant (TCA), specifically a secondary amine. In terms of its chemistry and pharmacology, maprotiline is closely related to such-other secondary-amine TCAs as nortriptyline and protriptyline and has similar effects to them, albeit with more distinct anxiolytic effects. Additionally, whereas protriptyline tends to be somewhat more stimulating and in any case is distinctly more-or-less non-sedating, mild degrees of sedation may be experienced with maprotiline.
Medical uses Maprotiline is used in the treatment of depression, such as depression associated with agitation or anxiety and has similar efficacy to the antidepressant drug moclobemide. This finding has also been validated by a group of general practitioners who compared the respective efficacy and tolerability of maprotiline and moclobemide. Treatment of depression of all forms and severities (endogenous, psychotic, involutional, and neurotic), especially depression associated with agitation or anxiety Panic disorder Neuropathic pain, including painful polyneuropathy in diabetics and non-diabetics alike. Treatment of the depressive phase of bipolar affective disorder For the symptomatic relief of anxiety, tension or insomnia
The use of maprotiline in the treatment of enuresis in pediatric patients has so far not been systematically explored and its use is not recommended. Safety and effectiveness in the pediatric population in general have not been established. Anyone considering the use of maprotiline in a child or adolescent must balance the potential risks with the clinical need.
A very small body of research has also explored the potential of maprotiline in treating diabetic kidney diseaseZhou, Z. and Liu, S., 2022. Maprotiline Ameliorates High Glucose-Induced Dysfunction in Renal Glomerular Endothelial Cells. Experimental and Clinical Endocrinology & Diabetes, 130(09), pp.596-603. and it has been measured against amitriptyline in this regard.
Maprotiline and fluoxetine have also been found, among certain lines of research, to have quite potent anti-profilerative effects against certain forms of cancer of the Burkitt lymphoma type. One study also bore ought a certain level of evidence regarding maprotiline’s ability to suppress both cholesterol biosynthesis and hepatocellular carcinoma liver-cancer progression.
Maprotiline was also measured against imipramine, fluoxetine and ketamine in an experiment-model involving two different kinds of chicken differently-conditioned against stress, including (black) Australorps in the proposed treatment of treatment-resistant depression in humans.
In general, lower dosages are recommended for patients over 60 years of age. Dosages of 50 mg to 75 mg daily are usually satisfactory as maintenance therapy for elderly patients who do not tolerate higher amounts. In any case, 225 m.g./d. is the absolute-maximum highest recommended dose for this drug, as any more can predispose more significantly to seizures. 150 m.g. is the average optimal daily dose for otherwise-healthy patients who can tolerate a full dose.
Available forms Coated tablets: 10 mg, 25 mg, 50 mg, and 75 mg Injectable concentrate, 25 mg
Contraindications In generalised theory, maprotiline (as with other tricyclic antidepressants, besides trimipramine and possibly clomipramine) may somewhat worsen certain features of schizophrenia, necessitating caution in prescribing them to someone with it and continuation of the antipsychotic treatment (e.g., with risperidone or olanzapine). However, certain bodies of evidence have found maprotiline a useful augment in treating some of the negative, or "anaesthetic", symptoms of schizophrenia and in probable extension pronounced schizoidia (including the characteristic deterioration in personal grooming/appearance). It has also been weighed against fluvoxamine in this overall regard (i.e., treating the negative symptoms of schizophrenia), with fluvoxamine evidencing clear superiority therein. Maprotiline, however, may be specifically useful for the "negative symptom" of alogia (poverty of thought and/or speech) and in this regard was found demonstrably superior to the other control-drugs (alprazolam, bromocriptine, citalopram, fluoxetine, fluvoxamine, nortriptyline) in one study. Citalopram, clomipramine and fluvoxamine appeared particularly useful in the study for reducing affective blunting, with alprazolam (Xanax) and maprotiline ranking joint-next.
Patients with bipolar affective disorder should not receive antidepressants whilst in a manic phase (including hypomania) under any circumstances whatsoever. (By the same analogy, people with schizoaffective disorder, bipolar type should not be taking maprotiline or other antidepressants while manic.) This is because antidepressants are known to come with the risk of worsening acute mania or precipitating it in so vulnerably-predisposed people.
They (antidepressants) may also negatively interfere with the treatment of mixed bipolar states (pure or schizo-affective), where electro-convulsive therapy (generally bilateral), valproate and antipsychotics prove more beneficial (lithium should not be administered concurrently with E.C.T. treatment, as it may induce severe confusion). However, maprotiline (at a high dose) was put to good use in one particular case, of one young man presenting with what was very-possibly a mixed-manic episode with a heavy preponderance of depressive symptoms (appearing as depression with significant narcissistic traits; including extrapunitive tendencies/blame-shifting, entitlement and interpersonal exploitation; and provisionally considered narcissistic depression). The maprotiline was combined with mirtazapine (low-dose), sodium valproate and aripiprazole.
Absolute Hypersensitivity to maprotiline or to other TCAs and TeCAs Hypertrophy of the prostate gland with urine hesitancy Closed angle glaucoma
Special caution needed Concomitant treatment with a MAO inhibitor Serious impairment of liver and kidney function Epilepsy and other conditions that lower the seizure threshold (active brain tumors, alcohol withdrawal, other medications) Serious cardiovascular conditions (arrhythmias, heart insufficiency, state after myocardial infarction etc.) Treatment of patients under age 18Simeon J, Maguire J, Lawrence S (1981). Maprotiline effects in children with enuresis and behavioural disorders. Progress in Neuro-Psychopharmacology 5 ( 5–6), 495–8
Suicidal patients As with other antidepressants, maprotiline increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of maprotiline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Maprotiline is not approved for use in pediatric patients.U.S. National Library of Medicine. Last Reviewed 1 Sept. 2010 Medline Plus entry for Maprotiline
Pregnancy and lactation Reproduction studies have been performed in female laboratory rabbits, mice, and rats at doses up to 1.3, 7, and 9 times the maximum daily human dose respectively and have revealed no evidence of impaired fertility or harm to the fetus due to maprotiline. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Maprotiline is excreted in breast milk. At steady-state, the concentrations in milk correspond closely to the concentrations in whole blood. Caution should be exercised when maprotiline hydrochloride is administered to a nursing woman.
Side effects The side-effect profile is comparable to other TCAs and TeCAS and many of the following are due to anticholinergic (which are less prominent than those of most TCAs) and antihistamine effects. Most often seen are: Dizziness Drowsiness Somnolence Fatigue Dry mouth (and complications of long-term uncontrolled dry mouth such as dental caries) Constipation Vertigo Nausea (rare, incidence of ~2%) and vomiting Increased appetite and weight gain Orthostatic hypotension, hypertension, sinus tachycardia, heart-block, arrhythmias and other cardiac effects Sexual dysfunction in men: impotence, priapism, delayed ejaculation, anejaculation, decreased libido Sexual dysfunction in women: decreased libido, vaginal dryness, painful sexual intercourse, anorgasmia Allergic skin reactions such as rash or urticaria (more often than with other antidepressants). Rarely, severe skin reactions such as erythema multiforme can occur. Photosensitivity Agitation, confusion Induction of hypomania or mania in patients with underlying bipolar affective disorder Psychotic symptoms Tremor Extrapyramidal symptoms Headache Seizures (at high doses) Rare haematological complications: leukopenia and agranulocytosis (dangerous fall in white blood cells) Fever Urinary retention
Maprotiline causes a strong initial sedation (first 2 to 3 weeks of therapy) and is therefore indicated to treat agitated patients or those with suicidal risks. It causes anticholinergic side effects (dry mouth, constipation, urinary hesitancy, etc.) with much lower incidence than amitriptyline. Originally, the manufacturer claimed that maprotiline is better tolerated than other TCAs and TeCAs. However, seizures, leukopenia and skin reactions occur more often with maprotiline than with comparable drugs (e.g., amitriptyline, protriptyline, mirtazapine). Indeed, seizures are greater risk for concern with maprotiline than with all other tricyclic antidepressants (rising from 75 mg, becoming significant at daily doses ≥ 200 m.g.), including clomipramine. It should thus be prescribed with particular, if not extreme, caution to people with a history of epilepsy/seizures of any other kind. In any case, the total daily dose should be kept to ≤ 225 milligrams.
Maprotiline has no known potential for abuse and psychological dependence.
Withdrawal Withdrawal symptoms frequently seen when treatment with maprotiline is stopped abruptly (agitation, anxiety, insomnia, sometimes activation of mania or rebound depression) can be avoided by reducing the daily dose of maprotiline gradually by approximately 25% each week. If treatment has to be stopped at once for medical reasons, the use of a benzodiazepine (e.g., lorazepam, clonazepam, diazepam) for a maximum of 4 weeks as needed will usually suppress withdrawal symptoms.
Interactions
Maprotiline does have a wide range of possible interactions. Some are typical for TCAs and TeCAs, others are caused by specific metabolic effects (e.g., high plasma-protein-binding) of maprotiline:
Increased drug actions: Other antidepressants, barbiturates, narcotics, sedating antihistamines, anticonvulsive drugs, alcohol resulting in increased central depression and necessitating some caution when using any of these drugs alongside maprotiline